We investigated in a well-established canine model of human sepsis the effects of two different techniques of sympathetic blockade during bacterial peritonitis on pain relief, hemodynamics and survival rate. Twenty-Two purpose-bred beagles (12-28 months, 10-12 kg) were studied. Fourteen animals received an epidural infusion of bupivicaine and morphine, and the other 8 either a celiac plexus block (n=4) or a sham block (n=4). Eighteen of the 22 animals received an intraperitoneal challenge of E. coli (1 ? 10 x 10^9 CFU?kg-1 bw). At comparable doses of intraperitoneal implanted E. coli (2.5 ? 5 x 10^9 CFU?kg-1 bw), the addition of sympathetic blockade produced a synergistic decrease in survival times (p=0.002) and mean left ventricular ejection fraction (p=0.008), and increase in creatinine levels (p=0.02). There was also a significant increase in TNF levels (p=0.004) and decrease in blood endotoxin clearance (p=0.006) associated with sympathetic blockade during sepsis. The celiac plexus blocked animals had no improvement in pain scores and subjectively looked clinically worse than septic animals without a celiac plexus block. In contrast, the epidural block was effective in blocking the pain and discomfort associated with low lethality doses of intraperitoneal bacteria reflected by no increase in pain scores compared to animals not receiving bacterial challenge. This study shows that, during severe bacterial peritonitis, maintenance of sympathetic tone irrespective of pain relief provided is necessary for clearance of bacterial toxins, control of proinflammatory mediator release, hemodynamic stability and survival. This study has presented two areas of further research. First, to understand the relationship between sympathetic tone and control of bacterial clearance and proinflammatory mediator release. Second, whether pain relief can be modulated to be effective without negatively effecting survival.